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Structural insights into the AapA1 toxin of Helicobacter pylori

dc.rights.licenseopenen_US
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
hal.structure.identifierRégulations Naturelles et Artificielles [ARNA]
dc.contributor.authorKORKUT, Dursun Nizam
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorALVES, Isabel
dc.contributor.authorVOGEL, Alexander
hal.structure.identifierRégulations Naturelles et Artificielles [ARNA]
dc.contributor.authorCHABAS, Sandrine
dc.contributor.authorSHARMA, Cynthia M.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorMARTINEZ, Denis
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLOQUET, Antoine
hal.structure.identifierInstitut Européen de Chimie et Biologie [IECB]
hal.structure.identifierRégulations Naturelles et Artificielles [ARNA]
dc.contributor.authorSALGADO, Gilmar F.
hal.structure.identifierRégulations Naturelles et Artificielles [ARNA]
dc.contributor.authorDARFEUILLE, Fabien
dc.date.accessioned2020-05-13T14:15:24Z
dc.date.available2020-05-13T14:15:24Z
dc.date.issued2019
dc.identifier.issn0304-4165en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/7566
dc.description.abstractEnBACKGROUND: We previously reported the identification of the aapA1/IsoA1 locus as part of a new family of toxin-antitoxin (TA) systems in the human pathogen Helicobacter pylori. AapA1 belongs to type I TA bacterial toxins, and both its mechanism of action towards the membrane and toxicity features are still unclear. METHODS: The biochemical characterization of the AapA1 toxic peptide was carried out using plasmid-borne expression and mutational approaches to follow its toxicity and localization. Biophysical properties of the AapA1 interaction with lipid membranes were studied by solution and solid-state NMR spectroscopy, plasmon waveguide resonance (PWR) and molecular modeling. RESULTS: We show that despite a low hydrophobic index, this toxin has a nanomolar affinity to the prokaryotic membrane. NMR spectroscopy reveals that the AapA1 toxin is structurally organized into three distinct domains: a positively charged disordered N-terminal domain (D), a single alpha-helix (H), and a basic C-terminal domain (R). The R domain interacts and destabilizes the membrane, while the H domain adopts a transmembrane conformation. These results were confirmed by alanine scanning of the minimal sequence required for toxicity. CONCLUSION: Our results have shown that specific amino acid residues along the H domain, as well as the R domain, are essential for the toxicity of the AapA1 toxin. GENERAL SIGNIFICANCE: Untangling and understanding the mechanism of action of small membrane-targeting toxins are difficult, but nevertheless contributes to a promising search and development of new antimicrobial drugs.
dc.description.sponsorshipRôle des systèmes toxine antitoxine de type I dans la persistence bactérienneen_US
dc.language.isoENen_US
dc.subject.enbacterial toxin
dc.subject.entoxin-antitoxin
dc.subject.enHelicobacter pylori
dc.subject.entransmembrane domain
dc.subject.ensmall membrane protein
dc.title.enStructural insights into the AapA1 toxin of Helicobacter pylori
dc.title.alternativebbagenen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.bbagen.2019.129423
dc.subject.halChimie/Matériauxen_US
bordeaux.journalBiochimica et Biophysica Acta (BBA) - General Subjectsen_US
bordeaux.page129423-129423en_US
bordeaux.volume1864en_US
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248en_US
bordeaux.issue1en_US
bordeaux.institutionBordeaux INPen_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03182187
hal.version1
hal.date.transferred2021-03-26T09:59:10Z
hal.exporttrue
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Biochimica%20et%20Biophysica%20Acta%20(BBA)%20-%20General%20Subjects&rft.date=2019&rft.volume=1864&rft.issue=1&rft.spage=129423-129423&rft.epage=129423-129423&rft.eissn=0304-4165&rft.issn=0304-4165&rft.au=KORKUT,%20Dursun%20Nizam&ALVES,%20Isabel&VOGEL,%20Alexander&CHABAS,%20Sandrine&SHARMA,%20Cynthia%20M.&rft.genre=article


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